Coulam C B, Razel A J, Kelalis P P, Svensson J, Spelsberg T C
Am J Obstet Gynecol. 1983 Nov 1;147(5):513-20. doi: 10.1016/0002-9378(83)90008-x.
Hypospadias represents a spectrum of disorders known as androgen insensitivity syndromes, which are characterized by a nonresponsiveness of an androgen target tissue to the steroid. The basic defect in this disorder is unknown. This article presents results of studies of the androgen receptor with use of human foreskin from normal neonates undergoing circumcision and from patients undergoing urethroplasty necessitated by hypospadias. It is speculated that a defect in receptor level or function might explain this disorder. The androgen receptors from both normal and hypospadiac tissue were stabilized with a buffer containing 50 mM Tris hydrochloride, 1 mM ethylenediaminetetraacetic acid, 12 mM monothioglycerol, 10% (v/v) glycerol, and 10 mM sodium molybdate plus 1 mM phenylmethylsulfonylfluoride (pH 7.5). The receptors were characterized by Scatchard analysis, competitive binding assays, sedimentation analysis, molecular sieve chromatography, and isoelectric focusing techniques. Specific R 1881 binding to soluble proteins from normal human foreskin was shown to be high affinity (dissociation constant = 0.5 nM), low capacity (6 fmol/mg of protein), and steroid specific. Sedimentation analysis by sucrose density gradients demonstrated the 8S-to-4S shift from low- to high-salt treatments. The receptor from the foreskins of hypospadiac patients also contained androgen receptor in a concentration similar to that in the foreskins of normal persons. The affinity for steroid binding and sedimentation profiles or sucrose gradients of the androgen receptor between normal persons and hypospadiac patients were also similar. However, the androgen receptor from hypospadiac patients displayed different patterns of molecular sieve chromatography from those displayed by the receptor of normal persons. The reason for this difference is not known but may reflect a defective receptor and explain the basic mechanism of this disorder.
尿道下裂是一种被称为雄激素不敏感综合征的一系列疾病，其特征是雄激素靶组织对类固醇无反应。这种疾病的基本缺陷尚不清楚。本文介绍了利用接受包皮环切术的正常新生儿以及因尿道下裂而需要进行尿道成形术的患者的人包皮对雄激素受体进行研究的结果。据推测，受体水平或功能的缺陷可能解释这种疾病。正常组织和尿道下裂组织中的雄激素受体均用含有50 mM盐酸 Tris、1 mM乙二胺四乙酸、12 mM单硫甘油、10%（v/v）甘油、10 mM钼酸钠加1 mM苯甲基磺酰氟（pH 7.5）的缓冲液进行稳定处理。通过Scatchard分析、竞争性结合测定、沉降分析、分子筛色谱和等电聚焦技术对受体进行了表征。结果表明，特异性R 1881与正常人包皮可溶性蛋白的结合具有高亲和力（解离常数 = 0.5 nM）、低容量（6 fmol/mg蛋白）且具有类固醇特异性。通过蔗糖密度梯度进行的沉降分析表明，从低盐处理到高盐处理，出现了8S到4S的转变。尿道下裂患者包皮中的受体所含雄激素受体的浓度与正常人包皮中的相似。正常人和尿道下裂患者之间雄激素受体的类固醇结合亲和力、沉降曲线或蔗糖梯度也相似。然而，尿道下裂患者的雄激素受体在分子筛色谱中呈现出与正常人受体不同的模式。这种差异的原因尚不清楚，但可能反映了受体存在缺陷，并解释了这种疾病的基本机制。
